10-Aza-11,12-secoprostaglandins

Abstract

This invention relates to 10-aza-11,12-secoprostaglandins and processes for their manufacture. These compounds have prostaglandin-like biological activity and are particularly useful as renal vasodilators.

What is claimed is: 
     
       1. The compound having the following formula: ##STR32##wherein R is carboxy or a carboxy salt having the formula --COO -  Me +  wherein Me is a pharmaceutically-acceptable cation derived from a metal or an amine; A is ethylene, trimethylene, α-methylethylene, β-methylethylene, α,α-dimethylethylene, or β,β-dimethylethylene;   R 1  is hydrogen or methyl;   R 2  is hydrogen or alkyl or 1-3 carbon atoms;   R 3  is hydrogen or methyl;   R 4  is hydrogen; and   R 5  is loweralkyl of 3-7 carbon atoms, 4-pentenyl, or 5,5,5-trifluoropentyl; except that when R 3  is methyl, R 5  is limited to propyl, butyl, pentyl, 4-methylpentyl, 4,4-dimethylpentyl, hexyl, heptyl, and 5,5,5-trifluoropentyl.   
     
     
       2. The compound of claim 1 which has the formula: ##STR33##wherein A is ethylene, α-methylethylene, β-methylethylene, trimethylene, α,α-dimethylethylene, or β,β-dimethylethylene; R 1  is hydrogen or methyl;   R 2  is hydrogen or alkyl having 1-3 carbon atoms; and   R 5  is loweralkyl of 3-7 carbon atoms, 4-pentenyl, or 5,5,5-trifluoropentyl.   
     
     
       3. The compound of claim 1 which has the formula: ##STR34##wherein A is ethylene, trimethylene, α-methylethylene, β-methylethylene, α,α-dimethylethylene, or β,β-dimethylethylene; R 1  is hydrogen or methyl;   R 2  is hydrogen or alkyl having 1-3 carbon atoms; and   R 10  is loweralkyl of 3-7 carbon atoms or 5,5,5-trifluoropentyl.   
     
     
       4. The compound of claim 2 wherein A is α-methylethylene, R 1  and R 2  are hydrogen and R 5  is pentyl, that is, 8-carbamoyl-12-hydroxy-2-methyl-heptadecanoic acid. 
     
     
       5. The compound of claim 2 wherein A is β,β-dimethylethylene, R 1  and R 2  are hydrogen and R 5  is pentyl, that is, 8-carbamoyl-12-3,3-dimethyl-heptadecanoic acid. 
     
     
       6. The compound of claim 2 wherein A is ethylene, R 1  and R 2  are hydrogen and R 5  is pentyl, that is, 8-carbamoyl-12-hydroxyheptadecanoic acid. 
     
     
       7. The compound of claim 2 wherein A is ethylene, R 1  is hydrogen, R 2  is methyl and R 5  is pentyl, that is, 8-methylcarbamoyl-12-hydroxyheptadecanoic acid. 
     
     
       8. The compound of claim 2 wherein A is ethylene, R 1  and R 2  are hydrogen and R 5  is 4-methylpentyl, that is, 8-carbamoyl-12-hydroxy-16-methylheptadecanoic acid. 
     
     
       9. The compound of claim 2 wherein A is ethylene, R 1  and R 2  are hydrogen and R 5  is heptyl, that is, 8-carbamoyl-12-hydroxynonadecanoic acid. 
     
     
       10. The compound of claim 2 wherein A is ethylene, R 1  and R 2  are hydrogen and R 5  is 5,5,5-trifluoropentyl, that is, 8-carbamoyl-12-hydroxy-17,17,17-trifluoroheptadecanoic acid. 
     
     
       11. The compound of claim 2 wherein A is ethylene, R 1  and R 2  are hydrogen and R 5  is 1,1-dimethylpentyl, that is, 8-carbamoyl-12-hydroxy-13,13-dimethylheptadecanoic acid. 
     
     
       12. The compound of claim 2 wherein A is ethylene, R 1  and R 2  are hydrogen, R 5  is pentyl and the 12-carbon is in the S configuration, that is, 8-carbamoyl-12(S)-hydroxyheptadecanoic acid. 
     
     
       13. The compound of claim 2 wherein A is ethylene, R 1  and R 2  are hydrogen, R 5  is pentyl and the 12-carbon atom is in the R configuration, that is, 8-carbamoyl-12(R)-hydroxyheptanoic acid. 
     
     
       14. The compound of claim 3 wherein A is ethylene, R 1  and R 2  are hydrogen and R 10  is pentyl, that is, 8-carbamoyl-12-hydroxy-12-methylheptadecanoic acid.